The focus of the proposed research is a continuation of efforts to improve the overall quantity of single-crystal x-ray diffraction results. X-ray diffraction crystallography remains one of the most powerful tools for determining the structures of molecules of all types, from simple inorganic compounds to complicated biological ones. During recent years the technique has become highly automated, such that almost the entire process - assigning the unit cell, collecting the diffracting data, solving the structure and refining the atom parameters - may be under computer control with only minimum human supervision. As a result, molecular structures can be determined very rapidly and, in most cases, with good accuracy and high precision. However, in a disturbingly large number of cases something goes wrong: the assigned unit cell is not the most appropriate, the solution of the structure leads to an incorrect space group, or the seemingly high precision masks, perhaps because of systematic errors, a low accuracy. It is the primary purpose of the proposed research to continue documenting these errors and bringing them to the attention of the crystallographic community, so that the need for increased care is apparent. At the same time, efforts will be made to pinpoint the sources of trouble, and to recognize those situations where special caution is warranted. Among these latter projects will be continued studies of the effects of systematic errors such as absorption and crystal misalignment on unit-cell parameters, and the effects of biasing the intensity data - perhaps by omitting the weaker reflections - on the final atom parameters. In short, continued studies will be made on methods of increasing both the reliability and the accuracy of this very powerful technique for biochemical research.